W. Mothes et al., SIGNAL SEQUENCE RECOGNITION IN COTRANSLATIONAL TRANSLOCATION BY PROTEIN-COMPONENTS OF THE ENDOPLASMIC-RETICULUM MEMBRANE, The Journal of cell biology, 142(2), 1998, pp. 355-364
We have investigated the role of membrane proteins and lipids during e
arly phases of the cotranslational insertion of secretory proteins int
o the translocation channel of the endoplasmic reticulum (ER) membrane
. We demonstrate that all steps, including the one during which signal
sequence recognition occurs, can be reproduced with purified transloc
ation components in detergent solution, in the absence of bulk lipids
or a bilayer. Photocross-linking experiments with native membranes sho
w that upon complete insertion into the channel signal sequences are b
oth precisely positioned with respect to the protein components of the
channel and contact lipids. Together, these results indicate that sig
nal sequences are bound to a specific binding site at the interface be
tween the channel and the surrounding lipids, and are recognized ultim
ately by protein-protein interactions. Our data also suggest that at l
east some signal sequences reach the binding site by transfer through
the interior of the channel.